Improved 1,1-disubstituted ethylene process

ABSTRACT

Improved iminium based processes for the production of cyanoacrylates and methylidene malonates wherein the improvement pertains to the presence of acid chlorides and/or acid anhydrides in the reaction mix.

RELATED APPLICATION

This patent application is a continuation of U.S. patent applicationSer. No. 14/628,273, filed Feb. 22, 2015, now U.S. Pat. No. 10,597,355,which is a continuation of U.S. patent application Ser. No. 13/752,384filed Jan. 28, 2013, now abandoned, which claims the benefit of expired,prior U.S. Provisional Patent Application No. 61/591,884 filed Jan. 28,2012, entitled Improved Methylidene Malonate Process, Gondi et. al., thecontents of all of which are hereby incorporated herein in theirentirety.

FIELD OF THE INVENTION

The present invention relates to a process for improving cure speedand/or providing more consistent, i.e., batch-to-batch, cure speed in1,1-disubstituted ethylene monomers and monomer containing compositions.The present invention also relates to an improved process for theproduction of 1,1-disubstituted ethylene monomers, including methylidenemalonates and cyanoacrylates, especially methylidene malonates, and theuse thereof.

BACKGROUND

1,1-disubstituted ethylene monomers and compositions containing the sameare well known and, for the most part, widely available. They haveutility in a broad array of end-use applications, most notably thosewhich take advantage of their cure or polymerizable properties.Specifically, they find broad utility in coatings, sealants andadhesives, among other applications. Those 1,1-disubstituted ethyleneshaving one or, preferably, two electron withdrawing substituents at the1 position have been used to provide adhesives and sealants with rapidcure rates and high bond strengths. Most notable among these are thecyanoacrylates such as ethyl cyanoacrylate and butyl cyanoacrylate.Another class of 1,1-disubstituted ethylenes that have demonstrated alot of promise, but have limited, if any, commercial success are themethylidene malonates, including diethyl methylidene malonate.

Commercial success of the 1,1-disubstituted ethylenes is reliant upon anumber of variables and factors including reasonable cost, high purity,good, especially long, shelf life and rapid cure rate. In an effort toachieve these goals, much work has been done to develop new and/orimproved processes and synthetic schemes for their manufacture,purification and isolation.

For example, α-cyano acrylates have been prepared (U.S. Pat. No.6,245,933) by reacting a cyanoacetate such as ethyl cyanoacetate withformaldehyde or a formaldehyde synthon such as paraformaldehyde in aKnoevenagel condensation followed by transesterification. The productmixture is then cracked and distilled to produce the α-cyano acrylatemonomer.

Similarly, extensive efforts have been undertaken over many decades inan effort to produce, on a commercially viable basis, methylidenemalonates. Two of the earliest methods for the production of dialkylmethylidene malonates, the simplest of the methylidene malonates, werethe iodide method in which methylene iodide was reacted with dialkylmalonates and the formaldehyde method in which formaldehyde was reactedwith dialkyl malonates in the presence of a base, in solution in alcoholsolvents. As an alternative, Bachman et al. (U.S. Pat. No. 2,313,501)taught the reaction of a C₁-C₅ dialkyl malonate with formaldehyde in thepresence of an alkali metal salt of a carboxylic acid, in solution in asubstantially anhydrous carboxylic acid solvent, followed by fractionaldistillation to separate the desired product. D'Alelio (U.S. Pat. No.2,330,033), on the other hand, alleged that such processes were erraticand more often produced yields that averaged 10 to 12 percent. D'Alelioespoused an improved process with yields on the order of 30% and higherby reacting a malonic acid ester with formaldehyde in a ratio of onemole of the former to at least one mole of the latter under alkalineconditions and, in most cases, in the presence of a polymerizationinhibitor such as copper, copper acetate, hydroquinone, resorcinol, orcatechol, to form a methylol derivative. The methylol derivative wasthen acidified to a pH below 7.0 using a suitable organic or inorganicacid in order to retard further reaction. The acidified mass is thendehydrated to form the corresponding methylidene malonate which issubsequently separated by distillation.

Not satisfied, Coover et al. (U.S. Pat. Nos. 3,221,745 and 3,523,097)took yet another approach to the formation of the methylidene malonates,electing to begin with a preformed dialkyl alkoxymethylenemalonate. Inaccordance with their process, the olefinic double bond of the lattercompound was subjected to hydrogenation in the presence of ahydrogenation catalyst and the hydrogenated compound was then subject topyrolysis in the presence of a phosphorous pentoxide inhibitor to stripoff the alcohol to produce the methylene malonate. The resultant masswas then subjected to vacuum distillation at low temperature to separatean allegedly high purity methylidene malonate, though with a low yield.According to Coover et al., the use of low temperature distillation issaid to prevent the contamination of the monomer with pyrolytic productsthat commonly result from high temperature distillation. These highpurity monomers are said to be especially important for surgicalapplications.

Eventually, such efforts led to multi-step processes in which certainunsaturated molecules served as a platform for the formation ofintermediate adducts from which the methylidene malonates weresubsequently stripped and recovered. For example, Hawkins et al. (U.S.Pat. No. 4,049,698) found that certain malonic diesters could be reactedwith formaldehyde and a linear, conjugated diene in the presence of aprimary, secondary or tertiary amine at about reflux temperature to forman intermediate adduct that could then be readily pyrolyzed attemperatures in excess of 600° C. to split off the desired methylidenemalonate. Similarly, Ponticello (U.S. Pat. No. 4,056,543) and Ponticelloet al. (U.S. Pat. No. 4,160,864) developed processes by whichasymmetrical methylene malonates, especially methyl allyl methylenemalonate, were prepared from previously formed norbomene adducts, thelatter having been prepared by the Diels-Alder reaction of an alkylacrylate with cyclopentadiene at room temperature or with heating or useof a Lewis catalyst. The so formed monoester norbomene adducts were thenreacted with an electrophile material in the presence of analkyl-substituted lithium amide complex to form the diester adduct andsubsequently pyrolyzed at a temperature of 400° C. to 800° C. at apressure of 1 mm to 760 mm Hg in an inert atmosphere to strip off thedesired methylene malonates.

Citing numerous disadvantages of the foregoing processes, whichdisadvantages were said to make them difficult, if not impossible, toadapt to industrial scale, Bru-Magniez et al. (U.S. Pat. Nos. 4,932,584and 5,142,098) developed a process whereby anthracene adducts wereprepared by reacting mono- or di-malonic acid ester with formaldehyde inthe presence of anthracene, most preferably in a non-aqueous solventmedium in the presence of select catalysts. According to Bru-Magniez etal., the anthracene adducts were said to be readily produced in highyields with the desired methylidene malonates obtained by stripping themfrom the anthracene adduct by any of the known methods including heattreatment, thermolysis, pyrolysis or hydrolysis; preferably heattreatment in the presence of maleic anhydride.

Despite all of these efforts, issues remained and commercial successwanting owing to continued process frustrations, instability andunpredictability. Malofsky et al. (WO 2010/129068) solved some of theproblems associated with process instability of the Retro-Diels-Alderadduct process by using polymerization inhibitors concurrent with orprior to stripping the adduct. Inhibitors such as trifluoroacetic acidand hydroquinone were used. In some examples, trifluoroacetic acid wasalso added to the distillate. Only limited curing studies were done, butthe resultant malonates were able to be polymerized withtetrabutylammonium fluoride. Malofsky teaches a variety of purificationprocesses including double distillation and extracting the product withan alkane such as n-heptane. Although this is an improvement over theart, these various purification processes can be costly and can reduceyield.

More recently, in an effort to find alternate and better routes toproducing 1,1-disubstituted ethylenes, a focus has been directed tocertain iminium based processes wherein select iminium salts are reactedwith various compounds containing a methylene linkage having attachedthereto at least one electron withdrawing group selected from nitriles,carboxylic acids, carboxylic esters, sulphonic acids, ketones or nitroto form electron deficient olefins. For example, McArdle et al. (WO2008/050313, U.S. Pat. App. Pub. 2009/0203934, and U.S. Pat. No.8,022,251) have taught the use certain specific iminium salts having atertiary carbon atom attached to a nitrogen atom in the production ofelectron deficient olefins, most especially cyanoacrylates, however,methylidene malonates are also mentioned. The preferred process involvedemploying the select iminium salts in producing the 2-cyanoacrylatesfrom nitriles such as ethyl cyanoacetate or malonitrile. When aformaldehyde derivative is used, the McArdle iminium salt can have thestructure I:

wherein R₃ is H, alkenyl, or alkynyl; R₄ is a hydrocarbon moietycomprising a tertiary carbon which is attached to the N atom, where thetertiary carbon atom is attached to or a part of one or moresubstituents selected from linear, branched, or cyclic alkyl or alkenyl,or one or more together form a cyclic structure; and X is an anion suchas a non-nucleophilic and/or an acidic anion. These imines may be formedby reacting formaldehyde or a source thereof with a primary amine havinga tertiary carbon atom attached to the nitrogen to form an imine whichis subsequently reacted with an acid under specified conditions to yieldan iminium salt. Variations and refinements of the iminium process aretaught in McArdle et al. (U.S. Pat. Nos. 7,659,423 and 7,973,119 andU.S. Pat. App. Pub. Nos. 2010/0210788 and 2010/0199888) and Bigi et al.(U.S. Pat. No. 7,718,821); the contents of all of which are herebyincorporated herein by reference.

The McArdle et. al. and Bigi et. al. iminium processes are not withouttheir shortcomings. Both require high temperature reactions,temperatures which can promote the in-situ polymerization of the monomerproduct. Additionally, these processes require specific amines to formthe iminium salts: amines that are oftentimes expensive and whosereaction byproducts are found, particularly in the case of methylidenemalonates, to promote unwanted reactions in-situ, including,specifically dimerization of the monomer. Further, these processes mustbe conducted at a very low pH in order to prevent the retro-conversionof the iminium salt back to the imine by loss of a proton. From theperspective of the formation of cyanoacrylate monomers, these factorsare of low concern, if any, as traditional processes for the productionof cyanoacrylates involves the formation of the polymer which is thencracked, typically at high temperature, to form the monomer and haveother issues that they too must content with. However, from theperspective of the formation of methylidene malonates, these factors areof considerable concern, particularly inasmuch as the yields and purityof the methylidene malonates so produced, as shown by McArdle et. al.,are still low.

Thus, despite the advances that have been made, there are stillimprovements to be made. More importantly, there still remains a needfor a commercially viable process for the production and isolation ofmethylidene malonates: a process which balances simplicity of processwith common or at least less costly materials with high yields andpurity and with consistency and repeatability.

SUMMARY OF THE INVENTION

The present invention provides for new and/or improved processes for theproduction of 1,1-disubstituted ethylenes, particularly methylidenemalonates and cyanoacrylates, most especially the methylidene malonates,and for the purification and isolation thereof as well as for the1,1-disubstituted ethylenes formed thereby. Each of these processespresents an improvement over existing iminium processes and produces1,1-disubstituted ethylenes quickly and efficiently in high yield andpurity and at relatively low cost, particularly as compared tonon-iminium processes and even certain known iminium processes.

According to a first aspect of the present teachings there is provided amethod of producing 1,1-disubstituted ethylenes which method comprisesreacting compounds containing a methylene linkage having attachedthereto at least one electron withdrawing group, especially thoseselected from nitriles, carboxylic acids, carboxylic esters, sulphonicacids, ketones or nitro, most especially the esters, especially thediesters, of malonic acid, with an iminium salt in the presence of anacid chloride and/or acid anhydride under appropriate conditions and foran appropriate time period to yield the corresponding 1,1-disubstitutedethylene. The iminium salts may be a pre-formed, isolated and/orpurified iminium salt or it may be an iminium salt that is formedin-situ by a process that is integrated into the overall reactionprocess for the production of the 1,1-disubstituted ethylene. In thelatter case, depending upon the specific iminium salt and its reactantsand reaction products, it is possible to directly combine the compoundcontaining the methylene linkage with the reaction product of theiminium reaction process, a product which, it is believed, inherentlycontains the iminium salt.

Suitable iminium salts generally correspond to the formula II

wherein R⁴, R⁵, R⁶ and R⁷ are each independently H or a hydrocarbon orsubstituted hydrocarbon moiety or a hydrocarbon, substituted hydrocarbonor heterohydrocarbon bridge whereby the nitrogen atom, the carbon, orboth of formula II are in a ring structure, preferably, R⁴, R⁵, R⁶ andR⁷ are each independently H or an alkyl, aryl, alkenyl or alkynyl; and Xis an anion, preferably a halogen, a non-nucleophilic anion, and/or aconjugate base of an acid, most preferably a halogen, a carboxylate or asulfonate. This process may be performed in the presence of a polar ornon-polar solvent or in a solvent-free process.

Preferred iminium salts are those wherein R⁴ and R⁵ are hydrogen (H) andR⁶ and R⁷ are each independently a hydrocarbon or substitutedhydrocarbon moiety, especially an alkyl, aryl, alkenyl or alkynylmoiety, most especially an alkyl moiety, and X is a halogen or asubstituted or unsubstituted carboxylate. In those instances where R⁶and/or R⁷ have a tertiary carbon atom attached to the nitrogen atom ofthe iminium salt, it is preferred that such be used in producing1,1-disubstituted ethylenes other than the methylidene malonates,particularly the cyanoacrylates: though again, they are suitable for themethylidene malonates as well. Especially preferred iminium salts arethose wherein R⁴ and R⁵ are hydrogen or alkyl, and both R⁶ and R⁷ arehydrocarbon moieties, especially alkyl. Most preferred are thedialkylmethylideneammonium halides and carboxylates, particularly thedialkyl methylideneammonium chlorides, acetates and haloacetates. Forpurposes of clarity, “alkyidene” refers to that portion of the iminiumcompound comprising:

Thus, an iminium compound wherein R⁴ and R⁵ are H and R⁶ and R⁷ aremethyl would be referred to as a dimethylmethylidene ammonium compound.

According to a second and preferred aspect of the present teachingsthere is provided a method of producing 1,1-disubstituted ethyleneswhich method comprises reacting an amine with an acid chloride and/or anacid anhydride, preferably at an equivalent excess of acid chlorideand/or acid anhydride relative to the methylene containing compound, toform an iminium reaction product, typically comprising an iminium salt,and then reacting that reaction product, with or without isolation orpurification, with a compound containing a methylene linkage havingattached thereto at least one electron withdrawing group selected fromnitriles, carboxylic acids, carboxylic esters, sulphonic acids, ketonesor nitro, most especially the esters, especially the diesters, ofmalonic acid, under appropriate conditions and for an appropriate timeperiod to yield the corresponding 1,1-disubstituted ethylene. Thisprocess too may be performed in the presence of a polar or non-polarsolvent or in a solvent-free process.

According to a third aspect of the present teachings there is provided amethod of producing 1,1-disubstituted ethylenes which method comprisesreacting compounds containing a methylene linkage having attachedthereto at least one electron withdrawing group selected from nitriles,carboxylic acids, carboxylic esters, sulphonic acids, ketones or nitro,most especially the esters, especially the diesters, of malonic acid,with an iminium salt or an iminium reaction product in the presence of anon-polar solvent for a sufficient time to yield the corresponding1,1-disubstituted ethylene wherein the anionic portion of the iminiumcompound or in-situ formed iminium reaction product is or is preparedfrom a carboxylate or an anhydride.

According to a fourth aspect of the present teachings there is providedan improved method of producing 1,1-disubstituted ethylenes involvingthe reaction of compounds containing a methylene linkage having attachedthereto at least one electron withdrawing group selected from nitriles,carboxylic acids, carboxylic esters, sulphonic acids, ketones or nitro,most especially the esters, especially the diesters, of malonic acid,with an iminium salt or an iminium reaction product wherein theimprovement comprises treating the 1,1-disubstituted ethylenic reactionproduct with a solid phase material known to adsorb or absorb polarmaterials in the presence of a non-polar solvent following completion ofthe reaction. If the reaction process to form the 1,1-disubstituteethylene is conducted in the presence of a polar solvent, one must firstremove and replace the polar solvent with a non-polar solvent. Treatmentwith the solid phase material is continued until most, if notsubstantially all, of the polar impurities are absorbed or adsorbed,after which the reaction product is then isolated/separated from thesolid phase material, e.g., by filtration, centrifugation, decanting,distillation, thin film evaporation, etc. Suitable solid phase materialsinclude ion-exchange resins, molecular sieves, zeolites, alumina, andthe like, provided that the same are acidic to neutral pH, preferablyacidic.

According to yet a fifth aspect of the present teachings there isprovided an improved method of producing 1,1-disubstituted ethylenesinvolving the reaction of compounds containing a methylene linkagehaving attached thereto at least one electron withdrawing group selectedfrom nitriles, carboxylic acids, carboxylic esters, sulphonic acids,ketones or nitro, most especially the esters, especially the diesters,of malonic acid, with an iminium salt or an iminium reaction productwherein the improvement comprises treating the isolated and/or purified1,1-disubstituted ethylene with a slightly acidic to mildly basicalumina and thereafter separating the alumina from the treated1,1-disubstituted ethylene.

Finally, it is also to be appreciated that the present teachings providefurther improvements in relation to the foregoing methods, whereby thefurther improvement lies in the practice of two or more of theaforementioned processes in a single process for the production of1,1-disubstituted ethylenes.

DETAILED DESCRIPTION

In accordance with the present teachings there are provided new and/orimproved processes or methods for the production of methylidenemalonates. All of these processes generally comprise the reaction of acompound containing a methylene linkage having attached thereto at leastone electron withdrawing group with a preformed or in-situ formediminium salt. As will be noted, there are several various processes andimprovements to existing processes disclosed herein that may be usedindividually or in combination, e.g., the improvements to existingmethods are also applicable to improve the new methods taught herein.

For purposes of convenience and expediency, unless otherwise obviousfrom the text, the term “ethylene precursor” shall refer to thecompounds containing the methylene linkage having attached thereto theone or more electron withdrawing groups. Similarly, unless contextdisallows, reference to the “iminium salt” shall refer to both apreformed iminium salt as well as the in-situ formed salt, whether in apurified or isolated state or as the reaction product of the reactantstherefore.

According to a first aspect of the present teachings there is provided amethod of producing 1,1-disubstituted ethylenes which method comprisesreacting ethylene precursors with an iminium salt in the presence of anacid chloride and/or acid anhydride under appropriate conditions, andpreferably in the presence of a polar or non-polar solvent, and for anappropriate time period to yield the corresponding 1,1-disubstitutedethylene.

According to a second and preferred aspect of the present teachingsthere is provided a method of producing 1,1-disubstituted ethyleneswhich method comprises reacting an amine with an acid chloride and/or anacid anhydride, preferably at an equivalent excess of acid chlorideand/or acid anhydride relative to the methylene containing compound, toform an iminium reaction product, typically comprising an iminium salt,and then reacting that reaction product, with or without isolation orpurification, with an ethylene precursor under appropriate conditionsand for an appropriate time period to yield the corresponding1,1-disubstituted ethylene. Each of the process steps of this secondaspect of the present teachings is preferably conducted in the presenceof a solvent, which may be polar or non-polar.

According to a third aspect of the present teachings there is provided amethod of producing 1,1-disubstituted ethylenes which method comprisesreacting an ethylene precursor with an iminium salt or an iminiumreaction product in the presence of a non-polar solvent for a sufficienttime to yield the corresponding 1,1-disubstituted ethylene wherein theanionic portion of the iminium compound or in-situ formed iminiumreaction product is or is prepared from a substituted or unsubstitutedcarboxylate or anhydride.

According to a fourth aspect of the present teachings there is providedan improved method of producing 1,1-disubstituted ethylenes involvingthe reaction of an ethylene precursor with an iminium salt wherein theimprovement comprises treating the 1,1-disubstituted ethylenic reactionproduct with a solid phase material known to adsorb or absorb polarmaterials in the presence of a non-polar solvent following completion ofthe reaction. If the reaction process to form the 1,1-disubstituteethylene is conducted in the presence of a polar solvent, one must firstremove and replace the polar solvent with a non-polar solvent. Treatmentwith the solid phase material is continued until most, if notsubstantially all, of the polar impurities are absorbed or adsorbed,after which the reaction product is then isolated/separated from thesolid phase material, e.g., by filtration, centrifugation, decanting,distillation, thin film evaporation, etc. Suitable solid phase materialsinclude ion-exchange resins, molecular sieves, zeolites, alumina, andthe like, provided that the same are acidic to neutral pH, preferablyacidic.

According to yet a fifth aspect of the present teachings there isprovided an improved method of producing 1,1-disubstituted ethylenesinvolving the reaction of an ethylene precursor with an iminium saltwherein the improvement comprises treating the isolated and/or purified1,1-disubstituted ethylene with a slightly acidic to mildly basicalumina and thereafter separating the alumina from the treated1,1-disubstituted ethylene.

In its most broad concept, the present teachings apply to the productionof 1,1-disubstituted ethylenes having at least one electron withdrawingsubstituent at the one position with the preferred electron withdrawinggroups being selected from nitriles (including cyano), nitro, carboxylicacids, carboxylic acid esters, sulphonic acids and esters, amides,ketones and formyl, especially cyano and carboxylic acid esters. Such1,1-disubstituted ethylenes generally correspond to the general formulaIII:

wherein R is H or C₁ to C₆ hydrocarbyl such as methyl, ethyl, ethenyl,propyl, propenyl, isopropyl, ispropenyl, butyl, or phenyl and X and Yare independently selected from C₁ to C₁₂, preferably C₁ to C₁₀, mostpreferably C₂ to C₈, hydrocarbyl or heterohydrocarbyl groups providedthat at least one of X and Y is a strong electron withdrawing group.Exemplary strong electron withdrawing groups include, but are notlimited to, cyano, carboxylic acid, carboxylic acid esters, amides,ketones or formyl and Y is cyano, carboxylic acid, carboxylic acidesters, amides, ketones, sulfinates, sulfonates, or formyl. Monomerswithin the scope of Formula I include α-cyanoacrylates, vinylidenecyanides, alkyl homologues of vinylidene cyanide, methylidene malonates,dialkyl methylene malonates, acylacrylonitriles, vinyl sulfinates, andvinyl sulfonates.

Exemplary preferred 1,1-disubstituted ethylene monomers of formula Iinclude, but are not limited to:

H₂C═C(CN)CO₂CH₂CH₃, H₂C═C(CN)CO₂(CH₂)₃CH₃, H₂C═C(CN)CO₂(CH₂)₅CH₃ andH₂C═C(CN)CO₂(CH₂)₇CH₃.

Exemplary preferred 1,1-disubstituted ethylene monomers are those of theformula IV:

where R² is H or —CH═CH₂, most preferably H; and X and Y are eachindependently —CN or —COOR³ wherein R³ is:

a hydrocarbyl or substituted hydrocarbyl group;

a group having the formula —R⁴—O—R⁵—O—R⁶, wherein R⁴ is a 1,2-alkylenegroup having 2-4 carbon atoms, R⁵ is an alkylene group having 2-4 carbonatoms, and R⁶ is an alkyl group having 1-6 carbon atoms; or

a group having the formula

wherein R⁷ is —(CH₂)_(n)—; —CH(CH₃)—; or —C(CH₃)₂— wherein n is 1 to 10,preferably 1-5, and R⁸ is H or an organic moiety, preferably ahydrocarbyl or substituted hydrocarbyl. Suitable hydrocarbyl andsubstituted hydrocarbyl groups include, but are not limited to, C₁-C₁₆,preferably C₁-C₈, straight chain or branched chain alkyl groups; C₁-C₁₆,preferably C₁-C₈, straight chain or branched chain alkyl groupssubstituted with an acyloxy group, a haloalkyl group, an alkoxy group, ahalogen atom, a cyano group, or a haloalkyl group; C₂-C₁₆, preferablyC₂-C₈, straight chain or branched chain alkenyl groups; C₂-C₁₂,preferably C₂-C₈, straight chain or branched chain alkynyl groups; andC₃-C₁₆, preferably C₃-C₈, cycloalkyl groups; as well as aryl andsubstituted aryl groups such as phenyl and substituted phenyl andaralkyl groups such as benzyl, methylbenzyl, and phenylethyl.Substituted hydrocarbyl groups include halogen substituted hydrocarbonssuch as chloro-, fluoro- and bromo-substituted hydrocarbons andoxy-substituted hydrocarbons such as alkoxy substituted hydrocarbons.

Those skilled in the art will readily appreciate the ethyleneprecursors, i.e., the compounds containing a methylene linkage andhaving attached thereto at least one electron withdrawing group,necessary to produce the desired 1,1-disubstituted ethylene as describedabove. Exemplary electron withdrawing groups include nitriles (includingcyano), nitro, carboxylic acids, carboxylic acid esters, sulphonic acidsand esters, amides, ketones and formyl. Preferred ethylene precursorsare those compounds having two or more electron withdrawing groups,wherein the electron withdrawing groups may be the same or different,for example, the ethylene precursor will have both a nitrile andcarboxylic acid ester withdrawing groups in the case of the productionof cyanoacrylate monomers. [0034] Representative ethylene precursorsinclude the malonitrile, malonic acid and its esters (including,particularly, its diesters), cyanoacetic acid and its esters (including,especially, the alkyl substituted acids and esters, e.g.,ethylcyanoacetate, butylcyanoacetate, octylcyanoacetate, etc.), ethylnitro acetate, Meldrum's acid and the like.

The present teachings are especially applicable to the reaction of theiminium salts with the cyanoacetates and the malonic acid esters. Theformer generally correspond to the formula V and the latter to theformula VI:

wherein, R¹ is H in the case of the mono-esters; otherwise R¹ and R² areeach independently a C₁ to C₁₈, preferably C₁ to C₁₂, more preferably C₁to C₆, hydrocarbon or heterohydrocarbon group, the latter having one ormore nitrogen, halogen, or oxygen atoms.

Preferably, R² is a C₂ to C₈ alkyl group in the case of thecyanoacetate. However, for many of the other ethylene precursors,especially the malonate esters, R¹ and R² are, preferably, bothhydrocarbon and/or heterohydrocarbon groups and represent a C₁ to C₁₀,more preferably a C₁ to C₆, linear or branched alkyl group; a C₃ to C₆alicyclic group; a C₂ to C₆ alkenyl group; or a C₂ to C₆ alkynyl group,either or both of which may be substituted with an ether, epoxide, halo,ester, cyano, aldehyde, keto or aryl group. Most preferably, both R¹ andR² are hydrocarbon or heterohydrocarbon groups wherein at least onecontains an ester linkage. In this regard, especially desirable diestersof malonic acid are those wherein at least one of the R¹ and R² groupsis of the formula:

—(CH₂)_(n)—COOR³

wherein R³ is a C₁ to C₁₇, preferably a C₁ to C₆ hydrocarbon orheterohydrocarbon group, the latter having one or more nitrogen,halogen, or oxygen atoms. Preferably, R³ is a C₁ to C₆, preferably a C₁to C₃, lower alkyl and n is an integer of from 1 to 5, preferably 1 or2.

Exemplary diesters of malonic acid include dimethyl malonate,diethylmalonate, di-isopropyl malonate, di-n-propyl malonate, and ethylmethyl malonate as well as those of the formula:

wherein R¹ and R³ are the same or different and represent a C₁ to C₃lower alkyl, especially ethyl.

The second critical reactant for the production of the 1,1-disubstitutedethylenes is the iminium. As noted above, these may be a pre-formedand/or isolated and/or purified iminium salts or it may be present as animinium salt or iminium salt reaction mix that is formed in-situ by aprocess that is integrated into the overall reaction process for theproduction of the 1,1-disubstituted ethylene. In the latter case,depending upon the specific iminium salt and its reactants and reactionproducts, it is possible to directly combine the ethylene precursor withthe reaction product of the iminium reaction process, a product which,it is believed, inherently contains the iminium salt.

Suitable iminium salts generally correspond to the formula II

wherein R⁴, R⁵, R⁶ and R⁷ are each independently H or a hydrocarbon orsubstituted hydrocarbon moiety or a hydrocarbon, substituted hydrocarbonor heterohydrocarbon bridge whereby the nitrogen atom, the carbon, orboth of formula II are in a ring structure, preferably, R⁴, R⁵, R⁶ andR⁷ are each independently H or an alkyl, aryl, alkenyl or alkynyl; and Xis an anion, preferably a halogen, a non-nucleophilic anion, and/or theconjugate salt of an acid, most preferably a halogen, a carboxylate or asulfonate. Generally speaking, if a hydrocarbon or heterohydrocarbonmoiety, R⁴, R⁵, R⁶ and R⁷ will have from 1 to 10, preferably from 1 to 6carbon atoms. Preferably, R⁴, R⁵, R⁶ and R⁷ are each independently H oran alkyl, aryl, alkenyl or alkynyl, most preferably alkyl. X is ananion, preferably a halogen, a non-nucleophilic anion, and/or theconjugate base of an acid, most preferably a halogen, a carboxylate or asulfonate. In those instances where R⁶ and/or R⁷ have a tertiary carbonatom attached to the nitrogen atom of the iminium salt, it is preferredthat such be used in producing 1,1-disubstituted ethylenes other thanthe methylidene malonates, particularly the cyanoacrylates: thoughagain, they are suitable for the methylidene malonates as well.

A group of preferred iminium salts are those wherein R¹ and R⁵ are bothhydrogen H and R⁶ and R⁷ are both H or at least one is H and the other ahydrocarbon or substituted hydrocarbon moiety, especially an alkyl,aryl, alkenyl or alkynyl moiety, most especially an alkyl moiety, and Xis a halogen or a substituted or unsubstituted carboxylate. Especiallypreferred iminium salts are those wherein R⁴ and R⁵ are hydrogen oralkyl, most preferably H or a C₁ to C₆ lower alkyl, and R⁶ and R⁷ areeach independently a hydrocarbon or substituted hydrocarbon moiety,especially an alkyl, aryl alkenyl or alkynyl moiety, most especially aC₁ to C₆ lower alkyl, and X is a halogen or a substituted orunsubstituted carboxylate. Most preferred are thedialkylalkylideneammonium halides and carboxylates, particularly thedialkylalkylideneammonium chlorides, acetates and haloacetates. Forpurposes of clarity, “alkidene” refers to that portion of the iminiumcompound comprising:

Thus, an iminium compound wherein R⁴ and R⁵ are H and R⁶ and R⁷ aremethyl would be referred to as a dimethylmethylidene ammonium compound.

The iminium salts may be formed by a number of alternative processes,all of which are well known in the art. One general route by which theymay be formed involves the preparation of the iminium salt from thecorresponding imine, which process may further involve the formation ofthe imine from select amines. Such processes are described in, e.g.,Abbaspour Tehrani and De Kimpe. Science of Synthesis, 27, 313 (2004),and references cited therein; Jahn and Schroth, Tett. Lett., 34(37),5863 (1993); M. B. Smith, Organic Synthesis, McGraw Hill International,Chemistry Series, 1302 (1994) and references cited therein; Hin, B.,Majer, P., Tsukamoto, T., J. Org. Chem., 67, 7365 (2002)] and in Mannichreactions [Holy et al, Tetrahedron, 35, 613 (1979); Bryson et al, J. OrgChem., 45, 524 (1980); and McArdle et. al., U.S. Pat. No. 7,569,719, allof which are incorporated herein by reference in their entirety.

Generally speaking, the iminium salts (also in the past referred to asimmonium salts) may be methanimimium salts, derived from formaldehyde;ternary iminium salts derived from aldehydes, e.g., acrolein; andquaternary iminium salts derived from ketones. Their preparations may beconducted with or without added catalyst provided that when a catalystis added, the catalyst should be one that is not solely a basicnucleophile. Thus, an acidic system would be preferred and a ditropicsystem may be used, as well.

Typically the imines from which the iminium salts are formed areproduced through the reaction of a carbonyl compound, especially analdehyde, and an amine, such as a primary amine like aniline,N-methylamine, or N-propylamine, which reaction results in the removalof water. Desirably, when a primary amine is used, the primary amineshould be one with some degree of steric hindrance, such as tertiarybutyl amine. The reaction of primary amine with carbonyl compound iswell known and can be a facile, high yielding reaction that may beconducted on a commercial scale e.g., see U.S. Pat. Nos. 2,582,128 and5,744,642, both of which are hereby incorporated herein by reference.

The so-formed imines from primary amines may be converted into iminiumsalts by contacting them with an acidic species, such as trifluoroaceticacid, acetic acid, sulphuric acid, methane sulfonic acid, or camphorsulfonic acid, and the like.

Another route to preparing the iminium salts is the use of secondaryamines wherein a secondary amine, such as dimethylamine, pyrrolidine,morpholine, and the like, are first converted to their respective saltsand then reacted with the carbonyl compound (with the removal of water)to produce iminium salts. Alternatively, the iminium salts can be formedby the reaction of chloromethyl ethers with N-(trimethylsilyl)amines.See e.g. Jahn and Schroth, Tett. Lett., 34(37), 5863 (1993) andAbbaspour Tehrani and De Kimpe, Science of Synthesis, 27, 313 (2004),and references cited therein.

Yet another route to preparing the iminium salts is the direct reactionof certain diamino compounds, such as 1,1-diaminoalkanes, especiallysubstituted diaminoalkanes, and the like with select activatingreagents, especially acid chlorides and acid anhydrides. Such processesare also well known. Especially preferred process of this route employN,N,N′,N′-tetraalkyl-1,1-diaminoaklanes, such astetramethyldiaminomethane and tetraethyldiaminomethane, as the startingamine.

It is also to be appreciated that many of the suitable iminium salts areavailable commercially, such as Eschenmoser's chloride and iodide saltswhich are available from The Aldrich Chemical Co.

Alternatively, and again as noted above, it is to be appreciated thatthe iminium salts may be formed in-situ, e.g., as an initial step orseries of steps in the production of the methylidene malonates.Specifically, rather than using purchased materials or separatelypreparing, isolating and purifying the iminium salt, the process ofpreparing the iminium salt is integrated into the overall methylidenemalonate production process. Here the iminium salt is formed (by any ofthe known methods, especially those noted above) and the ethyleneprecursor added to the iminium salt, or vice-versa. Depending upon thespecific process used to produce the iminium salt, it may be desirable,if not necessary, to isolate or consolidate the so formed iminium saltand/or to remove certain components of the reaction mix, especiallycatalysts in the case of those processes that employ the same, prior tocombining the iminium salt with the ethylene precursor.

Most preferably, it is desired to generate the in-situ formed iminiumsalt using those processes wherein the iminium salt is prepared directlyfrom the reaction of a 1,1-diamine compound and an activator whichcontributes the appropriate counter ion, either a halide or anon-nucleophilic conjugate base of an acid. Exemplary anion speciesinclude, but are not limited to, chloride, bromide, iodide, AsF₆, SbF₆,PF₆, BF₄, CH₃SO₃, CF₃SO₃, benzenesulfonate, para-toluenesulfonate,sulfate, bisulfate, perchlorate, SbCl₆, SbCl₃, SnCl₅, carboxylate, andsubstituted carboxylate. Generally, the amount of diamine to activatorto be used in the reaction process is a molar equivalence, though theamine may be used at a slight excess relative to the malonate startingmaterial. Most preferably, though, the activator is employed at a molarexcess as compared with the diamine. For example, the molar ratio(activator:diamine) of 1.0:1 to 10:1, more preferably from 1.2:1 to 5:1and most preferably from 1.5:1 to 2:1, may be used. These reactionprocesses occur rapidly and, for the most part, spontaneously:oftentimes requiring cooling to control the exotherm. These reactionsare also preferred as the product iminium salt can be used as is anddoes not require isolation and/or purification. [0050] The preferrediminium salts are the halide salts and the carboxylate salts: though asnoted and demonstrated, iminium salts of other anionic species areeffective as well. It is also thought that certain benefits may resultfrom the presence of the soft anion (as classified by Pearson'sPrinciples of Hard and Soft Acid Base (HSAB)). In following, althoughnot limited thereto, it is especially preferred that the carboxylateanion is an acetate, a propionate, a pivalate, a stearate, anisobutyrate, or a benzoate; most preferably an acetate.

For purposes of convenience, the present teachings will be discussed interms of the dialkylmethylideneammonium carboxylate salts, especiallythe dimethylmethylideneammonium carboxylate salts. However, it is to beappreciated and intended that these teachings are equally applicable toand reflective of the iminium carboxylate salts in general as well asthe other iminium salts mentioned above: all of which are suitable foruse in the practice of the present process. While not wanting to bebound by theory, it is thought that marked benefit in performance notedwith the carboxylate anion, especially in those iminium salts of FormulaVI above where R⁴ and R⁵ are H and, optionally, though preferably,neither R⁶ nor R⁷ contain a tertiary carbon atom bonded to the N atom,occurs as a result of improved solubility.

The dialkylmethylideneammonium carboxylates may be prepared by a varietyof methods. For example, they can be prepared by reacting the desiredtrialkylamine N-oxide with the acid anhydride of the desired carboxylateanion. Alternatively, the desired dialkylamine can be reacted withformaldehyde or a formaldehyde synthon such as paraformaldehyde in thepresence of the carboxylic acid. One preferred method is to prepare thedialkylmethylideneammonium carboxylate by an anion exchange reactionwith another more common and, preferably, cheaper,dialkylmethylideneammonium salt such as the commercially availabledimethylmethylideneammonium halides, especially the iodide (i.e.,Eschenmoser's salt).

More preferably, the dialkylmethylideneammonium carboxylate is preparedby the reaction of tetraalkyldiaminomethane with a carboxylic acidanhydride, e.g., dimethylmethylideneammonium carboxylate is prepared bythe reaction of tetramethydiaminomethane with a carboxylic acidanhydride. When this method is employed, the molar ratio oftetraalkyldiaminomethane to carboxylic acid anhydride is preferably from1.0:1 to 10:1, more preferably from 1.2:1 to 5:1 and most preferablyfrom 1.5:1 to 2:1. This reaction is preferably conducted in the presenceof a solvent such as acetonitrile or toluene. The process is preferablyconducted at and, because the reaction is typically exothermic,maintained at a reaction temperature of between 0° C. to 60° C. Thoughnot critical, it is preferable for reaction control that the carboxylicacid anhydride is added to the tetraalkyldiaminomethane as opposed tolatter being added to the former. Furthermore, because the reaction isexothermic, it is preferred to perform the addition gradually or inportions. Exemplary carboxylic acid anhydrides include acetic anhydride,propionic anhydride, isobutyric anhydride, pivalic anhydride, andbenzoic anhydride. Preferably, the carboxylic acid anhydride is aceticanhydride because it is readily available and because any unreactedacetic anhydride and any reaction byproducts such as dimethylacetamideare easily removed. Reaction times vary depending upon the reactants andconditions; however, most often the formation of the iminium salt iscompleted within a few hours, generally within an hour to an hour and ahalf. Again, shorter or longer times may be necessary to bring thereaction to completion.

As noted above, the dimethylmethylideneammonium carboxylate may beprepared en-mass or acquired and stored for use. However, for costconvenience and overall simplicity and consolidation of process, it isdesirable to employ an in-situ formed dimethylmethylideneammoniumcarboxylate, with or without isolation from its reaction mix. Here, forexample, the dimethylmethylideneammonium carboxylate is formed and,without isolation, combined with a diester of malonic acid and allowedto react.

The 1,1-disubstituted ethylene is prepared by combining the iminium saltor the in-situ formed iminium salt reaction product with the ethyleneprecursor. Although either may be added to the other, it is preferablethat the ethylene precursor is added to the iminium salt. The reactionis typically, and preferably, performed at a temperature from 0° C. to60° C., most typically at room temperature or higher. Highertemperatures can be used and tolerated, but such higher temperatures canresult in polymerization or partial polymerization and/or viscosityincrease of the formed 1,1-disubstituted ethylene monomer, which resultsin decreased yields and purity. Similarly, temperatures lower than 0° C.may be used but are not necessary and add to the overall productioncosts associated with the longer reaction times and the cooling of thereaction system. Furthermore, it is to be appreciated that the specificiminium salt or iminium salt reaction product may also influence thetemperature at which the reaction process is carrier out. For example,the presence of excess acid chlorides resulting from the in-situformation of the halide salts is found to slow the reaction somewhat.Accordingly, elevated temperatures, generally in the range of from 40°C. to 50° C. appear to provide optimal reaction for those salts.Similarly, the reaction appears slower with certain carboxylate salts,again suggesting a desire for elevated temperatures. On the other hand,certain halide salts, such as the Eschenmoser's salts, perform well atroom temperature.

The amount of reactants to be employed depends, in part, upon theselected reactants themselves and the impact, if any, of excess on theresultant product or process. Generally speaking, the ratio (on anequivalence basis) of iminium salt to ethylene precursor is from about1:1 to 10:1, preferably from about 1:1 to 6:1, most preferably, from aneconomic standpoint, 1:1 to 1:4. Again, it is to be appreciated thatcertain combinations of reactants will require higher or lower ratio toreach completion, even higher than the stated ranges.

Although not a requirement, it is preferred that the reaction of thereaction of the iminium salt and the ethylene precursor is carried outin the presence of a solvent. Indeed, if the iminium salt is formedin-situ, it is preferable that the iminium salt also be prepared in asolvent, most especially the same solvent as is to be employed for theoverall reaction. Preferable solvents have a boiling point atatmospheric pressure of between 40° C. and 150° C. Solvents with lowerboiling points can cause difficulty and reaction instability because thereaction is exothermic, or in some cases too slow and require heating.Solvents with higher boiling points can be difficult to remove insubsequent purification steps. Furthermore, as noted above, where theiminium salt is formed in-situ, it is preferred that the same solvent isused for both its preparation as well as in the reaction with theethylene precursor.

The solvents employed may be polar or nonpolar solvents. Exemplary polarsolvents include, but are not limited to, DMF, THF, acetonitrile, DMSO,IPA, ethanol and the like. Exemplary nonpolar solvents include, but arenot limited to, toluene, benzene, diethylether, hexane, cyclohexane andcarbontetrachlonde. Polar solvents appear to be optimal for reactionperformance in preparing the methylidene malonate; however, posedifficulties in the subsequent work-up to purify and isolate themethylidene malonate. In this respect, it is more difficult to removethe polar byproducts from the reaction. On the other hand, nonpolarsolvents do not provide optimum reaction performance, but make work-upand isolation and purification much simpler and more efficient. It isalso to be appreciated that one can conduct the reaction in a polarsolvent and then switch the solvent to a nonpolar solvent beforeperforming any steps to isolate and/or purify or treat the methylidenemalonate monomer. Furthermore, it is preferred to use the lower boilingpoint solvents since the higher temperatures needed for distillation ofreaction mixes with higher boiling point solvents may lead topolymerization and/or degradation of the monomer.

Generally speaking the amount of solvent to be used is from about 5× toabout 30×, preferably about 10× to about 25×, most preferably, on aneconomic and environmental basis, about 15× to about 20×, the amount ofmalonic acid ester, on a volumetric basis.

Reaction times for the production of the methylidene malonates will alsovary depending upon the reactants, reaction temperature, and the choiceof solvent. Reaction times range from under an hour to many hours,indeed 20 or more hours may be necessary to attain complete reaction.Typically, a reaction time of an hour or so up to six hours is suitableand sufficient.

Likewise, though not a requirement, it is preferred that the reaction ofthe ethylene precursor and the iminium salt occurs in the presence of anacid or its anhydride, preferably an acid having a pKa less than 6.0,more preferably less than 5.0. This is especially so for the reactioninvolving carboxylate ester ethylene precursors, most especially whenthe ethylene precursor is a malonic acid ester or diester. The presenceof the acid or anhydride is believed to stabilize the 1,1-disubstitutedethylene monomer product from polymerization. Suitable acids andanhydrides for preventing the polymerization of 1,1-disubstitutedethylene monomers are well known and discussed at length in Malofsky et.al. (US WO 2010/129068), which is hereby incorporated herein byreference in its entirety. Exemplary acids and anhydrides include, butare not limited to, acetic acid, acetic anhydride, trifluoroacetic acid,alkyl sulfonic acids such as methanesulfonic acid ortrifluoromethanesulfonic acid, arylsulfonic acids such astoluenesulfonic acid, and sulfuric acid. When used, the amount of acidto be added to the reaction mix is preferably from about 100 to about20,000 ppm, preferably from about 300 to about 10,000 ppm, mostpreferably from about 2000 to about 5000 ppm based on the amount of thediester of malonic acid. Optimum levels of acid to be added to a givenreaction mix can be determined by simple experimentation.

Additional stabilization may be imparted to the reaction mix, especiallyfollowing or towards the end of the reaction, by the addition of one ormore free radical polymerization inhibitors. The free radical stabilizeror polymerization inhibitor, as they are more commonly referred, may beadded alone or in combination with the acid stabilizer, or any anionicpolymerization inhibitor, again as mentioned in Malofsky et. al.Suitable free radical inhibitors include, but are not limited to, thehydroquinones and various hindered phenols, especially para-hydroquinonemonomethyl ether, catechol, pyrogallol, benzoquinones, 2-hydroxybenzoquinones, t-butyl catechol, butylated hydroxy anisole (BHA),butylated hydroxy toluene (BHT), t-butyl hydroquinones,2,2″-methylene-bis (6-tert-butyl-4-methylphenol), and mixtures thereof.The amount of free radical inhibitor to be added to the system shouldgenerally be from about 100 to about 20,000 ppm, preferably from about300 to about 10,000 ppm, most preferably from about 2000 to about 5000ppm based on the amount of the diester of malonic acid. As with the acidstabilizer, the optimal amount of free radical polymerization inhibitorto be used can be determined by simple experimentation.

The 1,1-disubstituted ethylenes formed by the reaction of the ethyleneprecursors and the iminium salts may be used as-is, but are preferablysubjected to various separation, isolation and/or purification steps,all of which are well known in the art. Where the reaction is conductedin a solvent wherein the reaction product is highly soluble therein, itis preferable to replace the solvent with another solvent having no orless solubility properties for the formed 1,1-disubstituted ethylenemonomer. Again, insofar as isolation and purification of the monomer isconcerned, any of the known methods for purification of like organicmolecules can be employed; however, purification is preferably achievedby distillation, most preferably under reduced pressure as this allowsfor lower distillation temperatures. Like the concern with higherreaction temperatures, higher distillation temperatures increase thepotential for polymerization or partial polymerization of themethylidene malonate, thereby decreasing the yield.

As noted, it may be desirable to isolate the 1,1-disubstituted ethylenemonomer material from the reaction mix prior to purification, andespecially prior to use. Isolation helps remove unreacted reactants andreaction byproducts. Isolation can be performed by any of the methodsknown in the art for such purpose. For example, isolation may beconducted as a low temperature distillation under reduced pressure.Alternatively, isolation may be achieved by solvent washing andseparation, exemplary solvents include water. Yet another alternative isthe treatment of the crude reaction product with a solid adsorbent suchas alumina to remove unreacted reactants and reaction byproducts.Preferably, isolation is achieved by a combination of these techniques.

Following the teachings of Malofsky et. al., the isolation and/orpurification steps are preferably conducted in the presence of one ormore stabilizers/polymerization inhibitors, especially anionicpolymerization inhibitors, most especially acid polymerizationinhibitors, and/or free radical polymerization inhibitors, mostpreferably both. Suitable polymerization inhibitors are discussed aboveand, in more detail, in Malofsky et. al. which, again, is herebyincorporated hereby by reference in its entirety. Preferably the anionicstabilizer/polymerization inhibitor is an acid stabilizer, mostpreferably an acid having a pKa less than 2.0. Exemplary acids includetrifluoroacetic acid, alkyl sulfonic acids such as methanesulfonic acidor trifluoromethanesulfonic acid, arylsulfonic acids such astoluenesulfonic acid, and sulfuric acid.

Although the stabilizers may be used in any isolation process, they aremost preferably used in those isolation processes that involve elevatingor elevated temperatures or any other conditions that are know topromote, accelerate or initiate polymerization of 1,1-disubstitutedethylene monomer. In any event, stabilizers should, and preferably are,employed in the purification steps, with addition thereof to thedistillation pot as well as the collection or receiver vessel.Stabilizers are also to be added to the final collected materials toinhibit polymerization during subsequent storage. Generally speaking theamount of stabilizer (anionic polymerization inhibitor, free radicalpolymerization inhibitor or both) to be added to the 1,1-disubstitutedethylene monomer reaction product, crude reaction product and/orisolated product should be from about 100 to about 20,000 ppm,preferably from about 300 to about 10,000 ppm, most preferably fromabout 2000 to about 5000 ppm based on the amount of the1,1-disubstituted ethylene monomer. Preferred or optimal stabilizers orcombinations of stabilizers as well as the amount thereof to use can bedetermined by simple experimentation

Having disclosed the general aspects and reagents to be employed in thepresently taught and claimed process, attention now is directed to thespecific aspects, each of which are new and/or improvements over thestate of the art.

According to a one aspect of the present teachings, those processes inwhich an ethylene precursor is reacted with an iminium salt to form a1,1-disubstituted ethylenes is improved by the addition of an acidhalide, especially an acid chloride, and/or an acid anhydride to thereaction mix and/or product. The addition of the acid halide and/or acidanhydride has been found to reduce the formation of dimer. In thisregard, it is believed that the reaction process generates amines,especially secondary amines, like diethylamine and their salts, whichcatalyze or promote dimer formation. The addition of the acid halideand/or acid anhydride are believed to scavenge these amines, therebypreventing the formation of the dimers. The acid halide and/or acidanhydride may be added at any time, though it is especially beneficialto add it to the reaction mix before or during the reaction. The amountof acid halide and/or acid anhydride to be added is not so critical andcan be found by simple experimentation for a particular reaction system.Oftentimes an amount of up to a molar equivalent based on the amount ofiminium salt present is sufficient: though larger amounts could be used.Generally lesser amounts, e.g., 0.2 to 0.5 eq. will suffice.

Alternatively, one may achieve the foregoing benefit by generating theiminium salt is-situ and using an excess of an acid halide and/or acidanhydride in the iminium salt formation. By this method, in addition toforming the desired iminium halide or iminium carboxylate one also addsto the reaction mix sufficient acid halide and/or acid anhydride toscavenge the amines. In this instance, the molar ratio of acid halide oracid anhydride is generally higher than or at the higher end of theratio of activator to diamine discussed above. Here, it is preferredthat the molar ratio is from 1.2:1 to 10:1, preferably from 1.5:1 to7:1, and most preferably from 1.5:1 to 5:1, may be used.

Acid halides are well known and widely available. These generallycorrespond to the formulae R⁹C(O)X and R⁹SO₂Xwhere R⁹ is an aliphatic oraromatic hydrocarbon or substituted hydrocarbon, especially a C₁ to C₁₈,preferably a C₁ to C₁₂, more preferably a C₁ to C₆ hydrocarbon orsubstituted hydrocarbon, and X is fluorine, chlorine, bromine or iodine.Preferred acid halides are those wherein R9 is a C₁ to C₆ hydrocarbonand X is chlorine. Especially preferred are the acid chlorides, i.e.,those compounds having the foregoing formula wherein X is chlorine,including the acyl chlorides, the aroyl chlorides and the sulfonylchlorides. Exemplary acid chlorides include acetyl chloride, propionylchloride, isobutyryl chloride, trimethylacetyl chloride, benzoylchloride, and chloroacetylchloride

Similarly, acid anhydrides are well known and widely available. Theseare organic compounds that has two acyl groups bound to the same oxygenatom. Most commonly, the acyl groups are derived from the samecarboxylic acid and correspond to the general formula (R⁹C(O))₂O,wherein R⁹ is as defined above. Exemplary acid anhydrides include formicacid anhydride, acetic anhydride, propionic anhydride, butyricanhydride, valeric anhydride, caprilic anhydride, trifluroacetate,isobutyric anhydride, trimethylacetic anhydride, trifluoroaceticanhydride, and sulfonic acid anhydride.

Another aspect of the present teachings pertains to the select use ofiminium carboxylates, either preformed or formed in-situ, in theprocesses for the production of the 1,1-disubstituted ethylenes.Specifically, it has been found that the select use of the iminiumcarboxylates allows one to use non-polar solvents as the solvent for theiminium preparation and/or the reaction of the iminium salt and theethylene precursor. Although non-polar solvents do not, in manyinstances, provide for the optimal conversion of ethylene precursor to1,1-disubstituted ethylene, they do allow for more efficient andeffective separation, isolation and/or purification of the formed1,1-disubstituted ethylene monomer. This benefit manifest in severalrespect including better yields as extraction of the 1,1-disubstitutemonomer is easier and more complete than from polar solvents,particularly those monomers that are highly soluble in polar solvents.

Another advantage of the use of iminium carboxylates is the findingthat, in many, if not most instances, the reaction to form the1,1-disubstituted ethylenes can be conducted at room temperature orslightly elevated temperatures. This compares with many of the acidchlorides which have a tendency to slow the reaction down, oftentimesnecessitating elevated temperature reaction conditions, generally 30° C.to 65° C. and higher.

Although it is possible to perform a solvent swap, wherein a non-polarsolvent is substituted for a polar solvent following the reactionprocess, such processes are time consuming, require the use ofadditional materials, including expensive solvents like acetonitrile.Thus, it is especially beneficial to be able to use non-polar solventsfrom the outset: a practice that is enabled by the select use of iminiumcarboxylates.

Yet another feature of the present teachings is the finding that one canimprove yields and stability by treating the 1,1-disubstituted ethylenereaction product with a solid phase material known to adsorb or absorbpolar materials in the presence of a non-polar solvent followingcompletion of the reaction. If the reaction process to form the1,1-disubstitute ethylene is conducted in the presence of a polarsolvent, one must first remove and replace the polar solvent with anon-polar solvent. Treatment with the solid phase material is performedfollowing the reaction itself and prior to any further efforts toisolate, separate and/or purify the 1,1-disubstituted ethylene monomer.The treatment is continued until most, if not substantially all, of thepolar impurities are absorbed or adsorbed, after which the reactionproduct is then isolated/separated from the solid phase material, e.g.,by filtration, centrifugation, decanting, distillation, thin filmevaporation, etc. Suitable solid phase materials include ion-exchangeresins, molecular sieves, zeolites, alumina, and the like, provided thatthe same are acidic to neutral pH, preferably acidic. Acidic materialsare needed to prevent or guard against polymerization of the monomersince many of the 1,1-disubstituted ethylene monomers are base catalyzedor activated.

This treatment process will typically employ a large amount of the solidphase material, generally up to 100 wt % or more based on the monomer tobe treated. Typically, the amount is from about 30 wt % to about 80 wt%, preferably from about 40 wt % to about 70 wt %. The high amount is toenable faster scavenging of the impurities while minimizing exposure,particularly since the solid phase materials oftentimes adsorb or absorbTFA and other key stabilizers. Again, because of the high reactivity ofthe 1,1-disubstituted ethylenes, especially the cyanoacrylate monomerand the methylidene malonate monomers, it is best to complete thetreatment as quickly as possible, removing the solid phase material andthem up-stabilizing the monomer as necessary. The specific amount andtime of the solid phase material treatment will vary depending upon thesolid phase material itself, the reaction product being treated, thetemperature, etc.

Finally, another improvement to the method of producing1,1-disubstituted ethylenes using iminium salts comprises treating theisolated and/or purified 1,1-disubstituted ethylene with a slightlyacidic to mildly basic alumina and thereafter separating the aluminafrom the treated 1,1-disubstituted ethylene. This method is disclosed atlength in co-pending, co-filed US patent application entitled “Improved1,1-disubstituted Ethylene Process”, Mc Conville et. al. and pendingU.S. Provisional Patent Application No. 61/591,882, filed 28 Jan. 2012,the contents of which are hereby incorporated herein in their entiretyby reference.

Generally speaking, this method entails treating the isolated and/orpurified 1,1-disubstituted ethylene with an alumina having a pH, asmeasured in neutral water, of generally from about 5.0 to about 8.5,preferably from about 5.5 to about 8.5, more preferably from about 6.0to about 8.0, most preferably from about 6.5 to about 7.5. Typically,the alumina treatment is conducted at from about 0° C. to about 150° C.,preferably from about 20° C. to 70° C., for from about 5 minutes toabout 20 hours, preferably from about 10 minutes to 5 hours. Thequantity of alumina employed depends upon many factors, including themethod employed. Generally speaking, especially in batch processing, theamount of alumina is from about 0.5 to about 20 weight percent,preferably from about 2 to about 10 weight percent, based on the weightof the monomer. In the case of continuous processing, the amount ofalumina is determined by the retention time in the treatment containeror column. Specifically, one must ensure proper retention time in orderto ensure sufficient treatment or one may circulate the monomer throughthe column until the desired effect is realized.

By implementing the improved processes as set forth herein, one realizesmore consistent and improved yields. For example, one may attain crudeyields in excess of 50%, preferably in excess of 60%, more preferably inexcess of 80%, most preferably in excess of 90%, with purities of,generally, 60% or more, preferably 70% or more, more preferably 80% ormore, most preferably 90% or more. Owing to the initial high purity ofthe crude products, subsequent purification allows for the even higherpurity materials with a modest to minimal effect on yield. For example,purified yields in excess of 25%, preferably in excess of 30% withpurities of, generally, 90% or more, preferably 95% or more, morepreferably 98% and even 99% or more are readily attainable.

The 1,1-disubstituted ethylenes resulting from the present teachings arewell known, though not all have yet made it to commercial success. Thesemonomers may be employed in a number of organic syntheses and polymerchemistry applications. In particular, they are especially useful in thepreparation of various adhesive and sealant applications includingindustrial, commercial and consumer adhesive and sealant applications aswell as in medical adhesives, most especially skin bonding applicationsfor human and animal skin bonding. In light of the benefit of thepresent invention, it is believed that these compositions are nowcommercially viable as cost effective and stable formulations can now bemade.

EXAMPLES

Having described the invention in general terms, Applicants now turn tothe following examples in which specific combinations of reactants,solvents and reaction times were evaluated. These examples are presentedas demonstrating the surprising attributes of the improved processes ofthe present. These examples are merely illustrative of the invention andare not to be deemed limiting thereof. Those skilled in the art willrecognize many variations that are within the spirit of the inventionand scope of the claims.

Iminium Salts

A plurality of preformed and in-situ formed iminium salts were employed.The general structures of these salts were as follows:

Halogen based salts:

Carboxylate salts:

Sulfonate salts:

Monomer

Similarly, three different monomer substrates containing a methylenelinkage having attached thereto at least one electron withdrawing groupwere employed to further demonstrate the breadth of the presentteachings as follows:

DMDEE Test

In order to assess cure performance of the 1,1-disubstituted ethylenemonomers, a standardized test based on dimorpholinodiethyl ether(“DMDEE”) as a cure initiatorlactivator was developed. This standardizedtest allowed direct comparison from treated and untreated1,1-disubstituted ethylene monomers as well as between different typesof treatments and variations of the same types of treatments.Specifically, the cure characteristics of 1,1-disubstituted ethylenemonomers were assess by inducing the polymerization of the monomers inthe presence of DMDEE as follows:

To a tared 4 mL glass vial equipped with a magnetic stir bar, 55microliters of a 10% by weight solution of DMDEE in isopropanol isadded. The vial is reweighed to determine the weight of solution addedand monomer is added to the DMDEE solution while stirring to give 1 mLmonomer per 42.5 mg DMDEE solution. Stirring is continued for oneminute. The stir bar is removed and replaced with a thermocouple.Temperature is plotted versus time. The polymerization induction time istaken as the time in which the rise in temperature between twosuccessive data points (three point running average) first exceeds 0.5°C. A short induction time is indicative of a monomer that is suitablyactive for commercial use, i.e., will polymerize in a reasonable periodof time. A long induction time is indicative of a monomer that, mostlikely due to the presence of impurities which inhibit polymerization,that is unsuitable for commercial use owing to the lack ofpolymerization or a cure speed that is too slow to be of commercialutility.

Example 1—Eschenmoser's Iodide Salt (EIS)

6 eq. of EIS (Iminium B) and 0.1 eq. of TFA, were added to Malonate2.1.2 in 20 volumes of 19:1 DMF:IPA solvent. The mixture was stirred for12-24 hours at room temperature and produced an in-solution yield of˜30% of Methylidene Malonate 2.1.2. Analysis of the reaction productshowed considerable dimer formation as well.

Example 2—Reverse Addition

Malonate 2.1.2 dissolved in DMF was slowly added to 6 eq. of EIS(Iminium B) over a period of 2 hours with stirring at room temperature.A measurement was taken after 22 hours and it was found that anin-solution yield of Methylidene Malonate 2.1.2 of 45% had beenattained. A further 3 eq. of EIS dissolved in DMF was added after 22hours and the reaction continued at room temperature for an additional18 hours. The reaction product then showed an in-solution yield of 47%.Analysis of the reaction product continued to showed considerable dimerformation as well.

Example 3—Acid Chloride Addition

Malonate 2.1.2 dissolved in DMF was slowly added to 3 eq. of EIS(Iminium B) over a period of 2 hours with stirring. A measurement wastaken after 4 hours and it was found that an in-solution yield ofMethylidene Malonate 2.1.2 of 26% had been attained. 0.25 eq. of acetylchloride was then added to the reaction mix and the reaction continuedfor an additional 16 hours. The reaction product then showed anin-solution yield of 47%; however, the level of dimer was markedlyreduced after the addition of the acetyl chloride, indeed, even lowerthan was present before the addition of the acetyl chloride. It istheorized that the acid chloride prevents the dimer formation and mayactually reverse its formation, possibly via a retro Michael addition.

Example 4—Acid Chloride Addition and Higher Temperatures

Having noted that the addition of the acetyl chloride (AcCl) appeared toslow the reaction process at room temperature, another experiment wasconducted to consider the impact of higher temperature in combinationwith the acetyl chloride addition. To correlate the impact of the acetylchloride and temperature on the reaction and reaction products, bothpercent conversion of the Malonate 2.1.2 and the percent of MethylideneMalonate 2.1.2 in the reaction products were assessed: dimer typicallyaccounting for sizeable portion of the reaction product. The specificsteps and results are presented in Table 1.

The results shown in Table 1 clearly demonstrate the marked improvementin yield of the desired Methylidene Malonate 2.1.2 as a result of theaddition of the acetyl chloride. Higher temperature appeared toaccelerate the conversion; however, elevating the temperature too highwith the further addition of EIS led to a loss in the benefit of theacetyl chloride. Presumably, the added EIS led to additional dimerformation and/or degradation of the Methylidene Malonate 2.1.2.Additionally, it is to be recognized that acetyl chloride boils at52-55° C. and, thus, higher temperatures may lead to a loss in acetylchloride itself from the reaction pot.

TABLE 1 Percentage of Time Conversion Monomer in (hr) Comment (%)Products (%) 1 Malonate was added over 1 hr to 3 eq 46 55 EIS 3 Added0.25 eq of AcCl after 1 hr 33 73 6 Added additional 3 eq of EIS after 3hrs 38 75 7 Started heating to 40° C. 57 73 21 After 14 hr at 40° C. 6265 23 Added additional 0.25 eq AcCl 57 72 25 Added additional 3 eq EIS61 72 41 Heated to 50° C. 85 57

Example 5—In-situ Eschenmoser's Chloride Salt (ECS)

A series of experiments were run to assess both the ability to use anin-situ formed Eschenmoser's salt, in this case Eschenmoser's chloridesalt (ECS—Iminium A), in the production of 1,1-disubstituted ethylenesas well as the impact of varying the mole ratio of the salt formingingredients on the same. In this specific set of experiments the ECS wasformed by the reaction of varying amounts of acetyl chloride and 6 Eq.of tetramethyldiaminomethane (TMDAM) in DMF at 0° C. Following theformation of the ECS, Malonate 2.1.2 dissolved in DMF was slowly addedto the reaction product of the ECS formation and the mixture heated to60° C. The specific experiments and the results attained thereby arepresented in Table 2.

TABLE 2 Reaction Conversion Percentage of Monomer Run Eq of AcCl Time(hr) (%) in Products (%) 1 6.5 16 98 62 2 6.5 21 99 45 3 7.5 21 99  69*4 9 25 59 70 5 12 25 22 55 *this corresponds to an in-solution yield ofMethylidene Malonate 2.1.2 of 68% (% conversion times % Monomer inProducts)

Example 6—Use of Acetonitrile as Solvent

Given the relatively high boiling point of DMF, acetonitrile wasevaluated as an alternate polar solvent, as well as to assess whetherother polar solvents were suitable. In this experiment 300 ml ofacetonitrile was added to a three neck round bottom flash containing 6eq. TMDAM (56.2 g) and the mixture cooled in an ice bath to 2-3° C. 7.5eq. acetyl chloride (48.8 ml) was then added slowly at a rate wherebythe temperature of the reaction mix was maintained 20° C. After theaddition was completed, the mixture was removed from the ice bath andallowed to come to room temperature while stirring (˜1 hour). Once atroom temperature, 1 eq. of Malonate 2.1.2 monomer (20 g) dissolved inacetonitrile (5 ml) was slowly added. Once the addition was completed,the mixture was stirred for one hour at room temperature and then themixture heated to 60° C. and stirred for an additional 24 hours. Thisproduced a reaction product with a 97% conversion and an in-solutionyield of 80%, as determined by GC.

Once the reaction was complete, the crude reaction mix was cooled to 30°C. and 400 ml of MTBE added to precipitate/crash out the amine salts.The solids were removed by filtration (at continued cold temperature toavoid the salts from going back into solution/melting) and the remainingfiltrate was found to have an in-solution yield of 73%.

Example 7—Use of Different Acid Chlorides

A further series of experiments were conducted to assess the suitabilityof various acid chlorides in the iminium process. The same process asemployed in Example 6 was employed here as well with the exception ofthe acid chloride and the mole ratios of the same and the TMDAM. Thespecific experiments and the results attained thereby are presented inTable 3.

Substituting the propionyl chloride (Run 1) for the acetyl chloride(Example 6) while keeping everything else the same presented animmediate jump in yield of ˜5%. The yield jumped even higher when theamount of amine was reduced to 3 eq. and the amount of chloride reducedto 4.5 eq.

TABLE 3 In- Con- Solution TMDAM Acid Time version Yield Run (eq)Chloride (eq) (hr) (%) (%) 1 6

18 98 85 2 3

20 >99 91 3 2

20 90.5 82 4 3

20 98.6 80 5 3

20 97.5 89.9 6 3

20 99 94.4 7 2

20 78.5 —

Example 8—Procedure Using Acetonitrile with Work Up to Remove AmmoniumSalts

In this experiment 15 ml of acetonitrile was added to a three neck roundbottom flask containing 3 eq. TMDAM (1.4 g) and the mixture cooled in anice bath to 2-3° C. 4.5 eq. propionyl chloride (1.8 ml) was then addedslowly at a rate whereby the temperature of the reaction mix wasmaintained below 20° C. After the addition was completed, the mixturewas removed from the ice bath and allowed to come to room temperaturewhile stirring (˜1 hour). Once at room temperature, 1 eq. of Malonate2.1.2 monomer (1 g) dissolved in acetonitrile (5 ml) was slowly added.Once the addition was completed, the mixture was stirred for one hour atroom temperature and then the mixture heated to 60° C. and stirred foran additional 10 hours. This produced a reaction product with anin-solution yield of 91%, as determined by GC.

Once the reaction was complete, the crude reaction mix was concentratedto remove most of the acetonitrile. The remaining reaction productappeared as a viscous oil to which was added toluene and the mixturedistilled twice. The mixture was then dissolved in 10 volumes of tolueneand an equal amount of MTBE. The resultant slurry was then filtered toremove the solids leaving a solution of the methylidene malonate 2.1.2monomer at an in-solutions yield of 80%.

Example 9—Polar and Nonpolar Solvents with Acid Anhydride to PrepareIminium Salts

A series of experiments were run with polar (acetonitrile) and nonpolar(toluene) solvents. The general procedure for both types of solvents ispretty much the same and begins with the addition of 15 volumes of theselected solvent to 2 eq. of the diamine in a round bottom flask keptunder nitrogen atmosphere. The reaction mixture is then cooled to 0-5°C. using an ice bath and 3.5 eq. of the acid anhydride is added to thechilled reaction mix at a rate whereby the internal temperature neverexceeds 10° C. After the addition is complete, the mixture is removedfrom the ice bath and allowed to warm to room temperature, generallyover a period of 1-1.5 hours. A solution of the malonate to be convertedand 0.1 eq. sulfuric acid or trifluoroacetic avid (TFA) in 5 volumes ofthe same solvent is then slowly added to the reaction mixture at a ratesuch that the internal temperature never exceeds 25° C. Thereafter theprocesses differ with that process employing the polar solventcontinuing to react at room temperature for a few hours, typically lessthan 6. That process using the non-polar solvent, on the other hand,involved heating the reaction mix to 40° C. and allowing the reaction tocontinue to completion, generally 15-20 hours.

Table 4 presents the results attained with a number of different acidanhydride derived iminium salts/reaction products in accordance with thegeneral procedure of the preceding paragraph.

TABLE 4 Iminium Conditions In-solution salt (salt introduction) Solventyield (%) C In-situ synthesis from acetic Acetonitrile 68 anhydride EIn-situ synthesis from Toluene 27 isobutyric anhydride F In-situsynthesis from Toluene Not measured- trimethylacetic anhydride (89%conversion)

Example 10—Use of Iminium I for Methylidene Malonate 2.1.2 Preparation

Iminium I was generated from N,N,N′,N′-tetraethyldiaminomethane in amanner analogous to the in situ generation of Iminium C (see Example 9).Thus, 2.90 g of N,N,N′,N′-tetraethyldiaminomethane was dissolved inacetonitrile (30 mL) and the solution was cooled to 0-5° C. in anice-water bath. Acetic anhydride (3.28 g) was added, causing thetemperature to rise to ˜10° C. The ice bath was removed and the mixturewas stirred for ˜1 hr. The mixture was placed back in an ice-water bathand cooled back to ˜15° C. A solution of Malonate 2.1.2 (2.00 g) andtrifluoroacetic acid ((0.11 g) in acetonitrile (10 mL) was then addedand the ice-water bath was again removed. After warming to 20-25° C.,the mixture was stirred for an additional 2 hr, at which point thein-solution yield was measured at 67%.

Example 11—Use of Iminium J for Methylidene Malonate 2.1.2 Preparation

Iminium J was generated from N,N′,-dimorpholinomethane in a manneranalogous to the in situ generation of Iminium I (see Example 10). Thus,3.42 g of N,N′-dimorpholinomethane was dissolved in acetonitrile (30 mL)and the solution was cooled to 0-5° C. in an ice-water bath. Aceticanhydride (3.28 g) was added, causing the temperature to rise to ˜10° C.The ice bath was removed and the mixture was stirred for ˜1 hr. Themixture was placed back in an ice-water bath and cooled back to ˜15° C.A solution of Malonate 2.1.2 (2.00 g) and trifluoroacetic acid ((0.11 g)in acetonitrile (10 mL) was then added and the ice-water bath was againremoved. After warming to 20-25° C., the mixture was stirred for anadditional 2 hr, at which point the in-solution yield was measured at75%.

Example 12—Scavenger

320 ml of toluene and 1.1 eq. of TMDAM (13.8 ml) was added to a roundbottom flask and kept under nitrogen atmosphere. The reaction mixturewas then cooled to 0-5° C. using an ice bath and 2.5 eq. of the aceticanhydride (21.7 ml) was added to the chilled reaction mix at a ratewhereby the internal temperature never exceeds 10° C. After the additionwas complete, the mixture was removed from the ice bath and allowed towarm to room temperature, generally over a period of 1-1.5 hours. Asolution of 1 eq. Malonate 2.1.2 (20 g) and 0.1 eq. sulfuric aciddissolved in toluene (80 ml) was then slowly added to the reactionmixture at a rate such that the internal temperature never exceeds 25°C. (10-15 minutes). The reaction was sluggish at room temperature butimproved upon heating. On heating at 40° C., a conversion of ˜90% wasattained after 20 hours, with an in-solution yield of ˜62%.

The reaction mixture was cooled to room temperature and 0.1 eq.concentrated sulfuric acid (0.49 ml) added. 13.26 g acidic, activatedalumina (66 wt. %) was then added to the reaction mix and stirred atroom temperature for 1.5 hours to remove impurities, particularly, it isbelieved amine salt impurities. GC analysis before and after the acidicalumina treatment confirmed the removal of impurities. The so formedslurry is filtered and the filtrate up-stabilized with 0.05 eq. conc.sulfuric acid (0.295 μl) before being subjected to a rotary evaporatorat 20-22° C. under high vacuum to remove toluene. The crude product wasthen transferred to a distillation pot and up-stabilized with anadditional 0.05 eq. sulfuric acid before commencing distillation. Thepot was heated to 50° C. and maintained at that temperature under vacuumfor at least 30-45 minutes. It is believed that dimethylacetamide isproduced as a byproduct and this step will ensure its removal to avoiddecomposition of the product. On further heating, Methylidene Malonate2.1.2 was recovered at a pot temperature of 156° C., a head temperatureof 125° C. and a vacuum of 0.25 mmHg in a collection vessel containing0.05 eq. sulfuric acid. The isolated monomer product was 89.5% pure byGC analysis. A second distillation of the isolated product yielded 6 g(28%) of 98.8% pure Methylidene Malonate 2.1.2 monomer.

Portions of the isolated monomer were treated with neutral alumina(WN-3, 6.5 pH) at 40° C. for 20 minutes and induction times tested forthe treated and untreated monomer. The alumina treatment resulted in theDMDEE induction time dropping from 134 minutes for the untreated monomerto 37 minutes and less than 5 minutes after treatment with at 6.7 wt %and 20 wt %, respectively.

Example 13—Scavengers 2

Similar experiments were conducted using other scavengers including Amolecular sieves and ion-exchange resins such as Dowlex Amberlyst 15.Results indicated that these too removed some of the impurities, howeverthe acidic alumina appeared to be more effective.

Example 14—Malonate 2.2

Tetramethyldiaminomethane (TMDAM, 1.1 eq.) and acetonitrile (15 volumes)were added to a round bottom flask and kept under nitrogen. The reactionmixture was cooled to 0-5° C. using an ice-bath. Acetic anhydride (2.5eq.) was added to the chilled reaction mixture at a rate such that theinternal temperature never exceeded 10° C. After the addition wascomplete, the ice-bath was removed and the reaction was allowed to warmup to 20° C. over a period of 1-1.5 hours. A solution of Malonate 2.2 (1eq) and acid (trifluoroacetic acid) (0.1 eq.) was prepared inacetonitrile (5 volumes) and was added slowly at a rate such that theinternal temperature never exceeded 25° C. (time of addition=10-15minutes). The reaction was complete in two hours at room temperature andachieve an in-solution conversion of 76%.

Example 15—Cyanoacrylate

Tetramethyldiaminomethane (TMDAM, 1.1 eq.) and acetonitrile (15 volumes)were added to a round bottom flask and kept under nitrogen. The reactionmixture was cooled to 0-5° C. using an ice-bath. Acetic anhydride (2.5eq.) was added to the chilled reaction mixture at a rate such that theinternal temperature never exceeded 10° C. After the addition wascomplete, the ice-bath was removed and the reaction was allowed to warmup to 20° C. over a period of 1-1.5 hours. A solution of EthylCyanoacetate (1 eq) and acid (sulfuric acid or trifluoroacetic acid)(0.1 eq.) was prepared in acetonitrile (5 volumes) and was added slowlyat a rate such that the internal temperature never exceeded 25° C. (timeof addition=10-15 minutes). The reaction was complete in two hours atroom temperature and achieve an in-solution conversion of 99%.

Although the present invention has been described with respect toaforementioned specific embodiments and examples, it should beappreciated that other embodiments utilizing the concept of the presentinvention are possible without departing from the scope of theinvention. The present invention is defined by the claimed elements andany and all modifications, variations, or equivalents that fall withinthe spirit and scope of the underlying principles embraced or embodiedthereby.

We claim:
 1. A method of producing methylidene malonates andcyanoacrylates which method comprises (1) reacting (A) a1,1-diaminoalkane with (B) from a 0.2 to a 10 molar equivalent excess ofan acid halide and/or an acid anhydride to form an in-situ reactionproduct comprising an iminium compound according to the Formula II:

wherein R⁴ and R⁵ are both H and R⁶ and R⁷ are each independently a C₁to C₁₀ hydrocarbon or substituted hydrocarbon or together form a bridgewhereby the nitrogen atom, R⁶ and R⁷ together form a ring structure, and(2) reacting the in-situ reaction product which includes the excess acidhalide and/or acid anhydride with (C) (i) a malonic acid estercorresponding to the formula VI:

wherein R¹ is hydrogen (H) and R² is a C₁ to C₁₈ hydrocarbon orheterohydrocarbon group, the latter having one or more nitrogen,halogen, or oxygen atoms or both R¹ and R² are independently a C₁ to C₁₈hydrocarbon or heterohydrocarbon group, the latter having one or morenitrogen, halogen, or oxygen atoms or (ii) a cyanoacetate correspondingto the formula V:CH₂(CN)CO₂R²  V wherein R² is a C₁ to C₁₈ hydrocarbon orheterohydrocarbon group, the latter having one or more nitrogen,halogen, or oxygen atoms.
 2. The method of claim 1 wherein R⁶ and R⁷ ofthe in-situ formed iminium compound of Formula II are each independentlya C₁ to C₆ alkyl or alkenyl group and X is a halogen or carboxylateanion.
 3. The method of claim 1 wherein the molar equivalent excess ofacid halide and/or acid anhydride is from 0.2 to
 5. 4. The method ofclaim 1 wherein the molar equivalent excess of acid halide and/or acidanhydride is from 0.5 to
 2. 5. The method of claim 1 wherein neither ofR⁶ and R⁷ is a hydrocarbon moiety comprising a tertiary carbon attachedto the N atom, and X is a halogen, a carboxylate or a sulfonate anion 6.The method of claim 1 wherein compound (C) is a malonic acid ester (i)of formula VI and one or both of R¹ and R² are independently, a C₁ toC₁₀ linear or branched alkyl group, a C₃ to C₆ alicyclic group, a C₂ toC₆ alkenyl group, or a C₂ to C₆ alkynyl group, which groups may besubstituted with or contain an ether, epoxide, halo, ester, cyano,aldehyde, keto or aryl group.
 7. The method of claim 6 wherein neitherof R⁶ and R⁷ is a hydrocarbon moiety comprising a tertiary carbonattached to the N atom, and X is a halogen, a carboxylate or a sulfonateanion
 8. The method of claim 6 wherein at least one of R¹ and R² is ofthe formula:—(CH₂)_(n)—COOR³ wherein R³ is a C₁ to C₁₇ hydrocarbon orheterohydrocarbon group, the latter having one or more nitrogen,halogen, or oxygen atoms, and n is an integer of from 1 to
 5. 9. Themethod of claim 1 wherein the malonic acid ester is a mono-ester whereinR¹ is H.
 10. The method of claim 1 wherein the malonic acid ester is adi-ester wherein neither of R¹ or R² is H.
 11. The method of claim 1wherein compound (C) is a cyanoactetate (ii) of formula V and R² is a C₁to C₆ hydrocarbon.
 12. The method of claim 1 wherein the equivalentweight of iminium salt to malonic acid ester is from 1:1 to 10:1. 13.The method of claim 1 wherein the equivalent weight of iminium salt tomalonic acid ester is from 1:1 to 6:1.
 14. The method of claim 1 whereinan acid halide is present and is an acid chloride.
 15. The method ofclaim 14 wherein the acid chloride is selected from the group consistingof acetyl chloride, propionyl chloride, isobutyryl chloride,trimethylacetyl chloride, benzoyl chloride, and choroacetyl chloride.16. The method of claim 1 wherein an acid anhydride is present.
 17. Themethod of claim 16 wherein the acid anhydride is selected from the groupconsisting of acetic anhydride, propionic anhydride, isobutyricanhydride, trimethylacetic anhydride, trifluoroacetic anhydride, andsulfonic acid anhydride.
 18. The method of claim 1 wherein the reactionis conducted in the presence of a non-polar solvent.
 19. The method ofclaim 18 wherein the non-polar solvent is selected from the groupconsisting of toluene, benzene, diethylether, chloroform, hexane,cyclohexane and carbontetrachloride.
 20. The method of claim 1 furthercomprising a step (3) wherein a non-polar solvent solution of the1,1-disubstituted ethylenic reaction product of step (2) is treated withan acidic, activated alumina.